Mivacurium

[SH4:p242-p245]

Quick summary

 

 

Usage

• Short-acting nondepolarising NMBD

Structure

Structure

• Benzylisoquinolinium nondepolarising NMBDs

Structure-activity relationship

• Consists of 3 stereoisomers
  * Trans-trans, cis-trans, and cis-cis
• Trans-trans and cis-trans are two most active and equipotent
  --> Accounts for 92-96% of mivacurium chloride
• Cis-cis is only 1/10 the potency of the other two

Pharmacodynamics

Effects by systems

Muscle relaxation

• Mivacurium produce maximum single-twitch depression
  * Orbicularis oculi BEFORE adductor pollicis
• Suxamethonium produce maximum single-twitch depression at orbicularis oculi and adductor pollicis simultaneously
• Recovery occurs at orbicularis oculi before adductor pollicis
  * For both mivacurium and suxamethonium

NB:

• Muscle relaxation at orbicularis oculi correlates with paralysis of laryngeal adductor muscles and diaphragm

CVS

• CVS response is minimal for doses up to 2 x ED95 (i.e. 0.15 mg/kg)
• Doses of 3 x ED95 (0.20 mg/kg)
  --> Histamine release
  --> Decreased MAP (maximal within 1-3 minutes, lasting 1-3 minutes)

Pharmacokinetics (PK)

Absorption

IV

Metabolism

• Trans-trans and cis-trans isomers are hydrolysed by plasma cholinesterase
  * At a rate 88% that of suxamethonium (i.e. still very fast)
  --> Responsible for the short duration of action
• Cis-cis isomer is hydrolysed slowly, NOT by plasma cholinesterase
  --> Instead is cleared at a rate closer to intermediate-acting NMBDs

Metabolites

• Metabolites from hydrolysis include
  * Quaternary amino alcohols
  * Quaternary monoesters
  --> Both inactive at NMJ

Rate of metabolism

• Rate of hydrolysis by plasma cholinesterase depends on the plasma concentration of mivacurium
  --> The greater the concentration, the greater the rate of hydrolysis
• Increasing the dose has only a small impact on the duration of action
  * Unlike other nondepolarising NMBDs
• Recovery after infusion is
  * Independent of infusion duration
  * Comparable to recovery after single doses [PI]
• Duration of action is increased in patients with atypical plasma cholinesterase

Elimination

• 7% of mivacurium is excreted unchanged in urine
  --> Renal excretion is a minor pathway for clearance

Action profile

[SH4:p212,p242]

• Onset of action = 2 - 3 minutes
• Duration of action = 12 - 20 minutes
  * >25% of control twitch height
• Duration of action = 25 - 40
  * >0.9 in TOF ratio

Pharmaceutics

Presentation

• 20mg in 10mLs (2mg/mL)

Composition

• Active = Mivacurium chloride
• Inactive = HCl (for adjusting pH)
• No preservative added (Mivacron)
• pH = 4.5 (3.5 - 6.5) [PI]

Storage

• Store below 25 degrees Celcius

Clinical

Administration

• ED95 = 0.08 mg/kg
  * Or 0.07mg/kg (0.06-0.09 mg/kg) [PI]
  * 0.10 mg/kg in children 2-12 years old [PI]
• Initial dose = 0.15 mg/kg over 5 to 15 seconds
  --> Clinical effective NMJ blockade last for 15 - 20 minutes
  --> Recovery to 95% in 25 - 30 minutes
• Maintenance dose = 0.10mg/kg
  --> Provide another 15 minutes of additional blockade
• Infusion rate = 0.5 - 0.6 mg/kg/hour
  * Start when early evidence of recovery from initial bolus
  * Reduction up to 40% with isoflurane or enflurane

Contraindication/precautions

• Contraindicated in patients known to be homozygous for the atypical plasma cholinesterase gene
• Caution in patients with reactive airway disease (e.g.asthma)
  * Due to risk of bronchospasm secondary to histamine release

Interactions

Anticholinesterases

[SH4:p244]

• Neostigmine profoundly decrease plasma cholinesterease activity
  --> Interference with normal rapid spontaneous recovery
• But both neostigmine and edrophonium antagonise the effects of mivacurium
  * Edrophonium provides more rapid antagonism

Volatile anaesthetics

• Isoflurane and enflurane [PI]
  * Reduce dosage requirement by up to 25%
  * Prolong duration of action

Special consideration

Malignant hyperthermia

• Does not trigger MH

Paediatrics

• Clearance of mivacurium is faster in younger patients
• Faster onset, shorter duration and faster recovery [PI]
  * Maximum blockade in 2 minutes
• Higher dosage requirement (ED95 = 0.10mg/kg) [PI]
• Initial dose for paediatrics = 0.1-0.2 mg/kg is recommended [PI]

Elderly

• Onset time, duration of action, and recovery rate may be extended by 20-30%

Renal dysfunction

• Renal excretion is a minor clearance pathyway
• Renal failure is often associated with decreased plasma cholinesterase activity
  --> But clinically the prolongation of action is insignificant
• c.f. According to [PI]
  --> Clinically effective duration of blockade produced by mivacurium 0.15mg/kg is approximately 1.5 times longer in ESRF

Hepatic dysfunction

Liver disease is often associated with

• Decreased plasma cholinesterase activity
  --> Prolonged duration
• Increased ECF volume
  --> Increased Vd
  --> Less intense NMJ blockade
  --> Clinically patient may appear resistant
  * Also seen with pancuronium and atracurium

But otherwise onset of action is unchanged

According to [PI]
--> Clinically effective duration of blockade produced by mivacurium 0.15mg/kg is approximately 3 times longer in end-stage hepatic failure

Burns

• Burn injury decreases plasma cholinesterase activity
• Burn injury causes receptor-mediated resistance to effects of nondepolarising NMBDs
• Overall, the two effects cancel out
  --> Dosage unchanged
  * c.f. For other nondepolarising NMBDs, a higher dose is required

Trivia

History

 

Others

Brand name: Mivacron